TY - JOUR
T1 - HLA dependent immune escape mechanisms in B-cell lymphomas
T2 - Implications for immune checkpoint inhibitor therapy?
AU - Nijland, Marcel
AU - Veenstra, Rianne N.
AU - Visser, Lydia
AU - Xu, Chuanhui
AU - Kushekhar, Kushi
AU - van Imhoff, Gustaaf W.
AU - Kluin, Philip M.
AU - van den Berg, Anke
AU - Diepstra, Arjan
PY - 2017
Y1 - 2017
N2 - Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas. We describe a novel mechanism of immune escape in which loss of HLA-DM expression results in aberrant membranous invariant chain peptide (CLIP) expression in HLA class II cell surface positive lymphoma cells, preventing presentation of antigenic peptides. In HLA class II positive cases, HLA-DM expression was lost in 49% of cHL, 0% of NLPHL, 14% of DLBCL, 3% of PCNSL and 0% of testicular lymphomas. Considering HLA class I, HLA class II and HLA-DM together, 88% of cHL, 10% of NLPHL, 62% of DLBCL, 77% of PCNSL and 87% of testicular lymphoma cases had abnormal HLA expression patterns. In conclusion, an HLA expression pattern incompatible with normal antigen presentation is common in cHL, DLBCL, PCNSL and testicular lymphoma. Retention of CLIP in HLA class II caused by loss of HLA-DM is a novel immune escape mechanism, especially prevalent in cHL. Aberrant HLA expression should be taken into account when evaluating efficacy of checkpoint inhibitors in B-cell lymphomas.
AB - Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas. We describe a novel mechanism of immune escape in which loss of HLA-DM expression results in aberrant membranous invariant chain peptide (CLIP) expression in HLA class II cell surface positive lymphoma cells, preventing presentation of antigenic peptides. In HLA class II positive cases, HLA-DM expression was lost in 49% of cHL, 0% of NLPHL, 14% of DLBCL, 3% of PCNSL and 0% of testicular lymphomas. Considering HLA class I, HLA class II and HLA-DM together, 88% of cHL, 10% of NLPHL, 62% of DLBCL, 77% of PCNSL and 87% of testicular lymphoma cases had abnormal HLA expression patterns. In conclusion, an HLA expression pattern incompatible with normal antigen presentation is common in cHL, DLBCL, PCNSL and testicular lymphoma. Retention of CLIP in HLA class II caused by loss of HLA-DM is a novel immune escape mechanism, especially prevalent in cHL. Aberrant HLA expression should be taken into account when evaluating efficacy of checkpoint inhibitors in B-cell lymphomas.
KW - Diffuse large B-cell lymphoma
KW - Epstein barr virus
KW - human leukocyte antigen
KW - Hodgkin lymphoma
KW - immune checkpoint inhibitor
KW - immune evasion
KW - primary central nervous system lymphoma
KW - major histocompatibility complex
KW - therapy response
KW - CLASS-II EXPRESSION
KW - REED-STERNBERG CELLS
KW - CYTOTOXIC T-LYMPHOCYTES
KW - POOR PATIENT SURVIVAL
KW - COMPLEX CLASS-I
KW - HODGKINS-LYMPHOMA
KW - PROGNOSTIC-SIGNIFICANCE
KW - ANTIGEN PRESENTATION
KW - PROTEIN EXPRESSION
KW - DR EXPRESSION
U2 - 10.1080/2162402X.2017.1295202
DO - 10.1080/2162402X.2017.1295202
M3 - Article
C2 - 28507804
SN - 2162-4011
VL - 6
JO - OncoImmunology
JF - OncoImmunology
IS - 4
ER -